Annually, approximately 2 million Americans suffer a moderate to severe traumatic brain injury (TBI). These injuries produce enduring disabilities that include cognitive, sensory, motor, and emotional impairments. The associated health care costs from these injuries are staggering. Confounding this major public health issue is the fact that currently there are very few pharmacological treatment options for patients who have suffered TBI. In part, this occurs because many newly synthesized drugs fail in various stages of efficacy testing. Given the fact that newly synthesized drugs fail in clinical trials it seems reasonable to begin to examine the potential efficacy of more natural substances. It has recently been demonstrated that administration of vitamin B3 (B3) following experimentally induced stroke reduces the size of the infarct and can improve behavioral outcome in rats. In addition, the preclinical efficacy of magnesium pharmacotherapy has been well established. The proposed research will investigate the potential preclinical efficacy of B3 to lessen the physiological consequences of brain injury and improve behavioral outcome. We will use the rodent bilateral frontal cortical contusion injury model, which is similar to a frontal head injury sustained in a car accident. The specific aims of this study are to: 1) determine if administration of B3 following injury can significantly reduce the cognitive and sensorimotor impairments seen following TBI; 2) determine the best injections parameters (i.e., window of opportunity and dose response) for B3 pharmacotherapy following TBI; 3) determine if administration of B3 following injury can significantly decrease the amount of injury-induced edema and injury-induced magnesium depletion; 4) determine the effect of B3 pharmacotherapy on apoptosis and reactive gliosis following TBI. The research proposed here will determine if B3 holds any preclinical efficacy for the treatment of TBI and begin to define the parameters for the development of B3 as a clinical treatment for TBI. [unreadable] [unreadable]